Table 1.
Studies addressing the genomic profiling of young patients with lung cancer from 2010 to 2020
| Manuscript, location | Age cut-off (years) | Population | Technique | Oncogenic genomic alteration (%) | EGFR (%) | ALK (%) | ROS1 (%) | BRAF (%) | RET (%) | HER2 (%) | Other (%) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Tian et al., 2020 West China Hospitala |
50 | NSCLC− ALK+. N = 101 Y = 52 |
NGS | – | – | EML4-ALK: 80.8 versus 79.6 EML4-ALK v1: 38.5 versus 14.3; P < 0.01 EML4-ALK v2: 1.9 versus 8.2 P = 0.19 EML4-ALK v3: 28.9 versus 40.8; P = 0.21 Non-EML4-ALK: 19 versus 21; P = 1.0 ALKm/TP53 mut: 34.5 versus 13.3; P = 0.07 |
– | – | – | – | – |
| Yang et al., 2019 Zhejiang Cancer Hospitala |
40 | Localized NSCLC N = 640 Y = 54 |
rtPCR | 76.7 versus 71.8; P = 0.49 | 48.8 versus 48 | 6.9 versus 3.3 | 6.9 versus 1.5 | 0 versus 1 | 9.3 versus 1 | 0 versus 2 | KRAS: 2 versus 5.6 PI3KCA: 2 versus 2 Fusion genes: 23.3 versus 5.9; P < 0.01 |
| Suidan et al., 2019 Davidoff Cancer Center, Rabin Medical Center, Israela |
50 | Lung cancer N = 186 Y = 62 |
rtPCR (24), NGS (78) |
63 versus 43 | 23 versus 18; P = 0.4 | 13 versus 2; P < 0.01 | – | – | – | – | Other genomic alterations (MET, KRAS, HER2, TP53, MYC, BRAF, BRCA1-2, APC): 27 versus 23; P = 0.45 |
| Pan et al., 2018 Jinling Hospital, China |
40 | NSCLC N = 272 LUAD N = 194 |
LUAD: rtPCR (EGFR) IHC (ALK) FISH (ROS1) |
– | 40 (29/73) | 34 (25/74) | 14 (1/7) | – | – | – | – |
| Hsu et al., 2016 National Taiwan Lung Cancer Registrya |
45 | Lung cancer N = 21536 Y = 1074 |
rtPCR, PCR, Sanger |
– | 52.5 versus 60.6; P < 0.01 | – | – | – | – | – | – |
| Wu et al., 2018 National Taiwan University Hospitala |
50 | Stage IV LUAD N = 872 Y = 142 |
rtPCR | 91 versus 84; P = 0.03 | 60 versus 67, P = 0.09 Uncommon mutations: 18 versus 9; P = 0.02 |
18.4 versus 5; P < 0.01a | 6 versus 1; P < 0.01 | 0.7 versus 1.6; P > 0.05 | 1.4 versus 2.1; P > 0.05 | 5 versus 2.7; P > 0.05 | KRAS: 0.7 versus 1.9; P > 0.05 PIK3CA: 0 versus 1.8 JAK2: 0 versus 0.6 |
| Wu et al., 2017 National Taiwan University Hospitala |
50 | LUAD N = 1039 Y = 161 |
rtPCR | – | 57.8 versus 66.1; P = 0.04 Uncommon mutations: 13.7 versus 8.4; P = 0.03 |
– | – | – | – | – | – |
| Hou et al., 2018 Hospital of Qingdao Universitya |
45 | Resected LUAD N = 177 Y = 87 |
NGS | 90.8 versus 85.6; P < 0.01 | 56.3 versus 52.2; P = 0.65 Concurrent TP53 mut: 81.6 versus 46.8; P < 0.001 |
16.1 versus 1.1; P < 0.01 | 0 versus 3.3; P = 0.24 | 3.4 versus 1.1; P = 0.36 | 1.1 versus 1.1; P = 1.0 | 13.8 versus 4.4; P = 0.03 | KRAS: 3.4 versus 18.9; P < 0.01 STK11: 1.1 versus 8.9; P = 0.03 MET: 0 versus 2.2; P = 0.49 TP53: 56.3 versus 48.9; P = 0.36 |
| Chen et al., 2019 First Affiliated Hospital, Zhejiang University |
35 | LUAD N = 89 |
NGS IHC for ALK and ROS1 |
67 | 21.3 | 16.9 | 1.1 | 3.4 | - | 24.7 | TP53: 9 PI3KCA: 1.1 |
| Chen et al., 2019 Affiliated Cancer Hospital of Zhengzhou Universitya |
40 | LUAD N = 1000 Y = 181 |
NGS | 84 versus 66; P < 0.01 | 34.3 versus 50.1 P < 0.01 Ex19del: 75.5 versus 40.2; P < 0.01 L858R: 16.1 versus 43.9; P < 0.01 G719X: 0 versus 4.6; P < 0.01 L861Q: 0 versus 2.4; P < 0.01 Ex20ins: 8.1 versus 1.2; P < 0.01 T790M: 0 versus 5.1; P < 0.01 |
37.6 versus 4.0; P < 0.01 | 1.7 versus 1.0; P = 0.25 | – | – | 2.2 versus 1.1; P = 0.23 | KRAS: 6.1 versus 10.4; P = 0.07 MET: 2.2 versus 0.2; P < 0.01 |
| Tanaka et al., 2017 Aichi Cancer Center Hospitala |
40 | LUAD N = 1746 Y = 81 |
NGS | 62 | 29.6 versus 45.4; P < 0.01 Ex19del: 75 versus 43; P < 0.01 L858R: 17 versus 48; P < 0.01 Ex20ins: 8 versus 1; P < 0.01 G719X: 0 versus 4; P = 0.32 L861X: 0 versus 1; P = 0.63 |
40.7 versus 4.2; P < 0.01 | 2.4 versus 0.001; P = 0.02 | 0 versus 0.4; P = 0.5 | 2.5 versus 0.01; P = 0.1 | 4.9 versus 1.1; P < 0.01 | KRAS: 2.2 versus 9.9; P: 0.02 |
| Sacher et al., 2016 Dana-Farber/Harvard Cancer Centera |
40 | NSCLC N = 2237 Y = 81 |
NGS, Sanger, PCR, FISH (ALK and ROS1) | 68 versus 52; P < 0.01 | 47 versus 40; P = 0.01 | 25 versus 1; P < 0.01 | 6 versus 1; P = 0.1 | 0 versus 3; P = 0.12 | – | 2 versus 3; P = 0.15 | KRAS: 9 versus 27; P < 0.01 |
| Yang et al., 2019 General Hospital of Chinesea |
36 | LUAD N = 44 Y = 20 |
Somatic and germline WES ALK IHC |
60 versus 58 | 35 versus 58.3; P = 0.12 | 25 versus 0; P = 0.50 | – | – | – | – | KRAS: 0 versus 8.3; P = 0.55 TP53: 35 versus 41.7; P = 0.88 FRG1: 40 versus 12.5; P = 0.08 KMT2: 50 versus 16.7; P = 0.04 N somatic mut/tumor: 92 versus 84; P: 0.42 |
| Kim et al., 2012 Inha University Hospital, Koreaa |
40 | NSCLC N = 1147 Y = 52 |
IHC for EGFR and ALK | 26 versus 31.9 | 22.6 versus 26.9; P = 0.60 | 3.2 versus 5.0; P = 0.86 | – | – | – | – | – |
| Wang et al., 2015 First Affiliated Hospital, Zhejiang University |
30 | Lung cancer N = 41 |
pyroPCR for EGFR FISH for ALK IHC for ROS1 |
68 | 22.7 | 27.2 | 11.7 | – | – | – | KRAS: 11.7 |
| Catania et al., 2015 Tumor Registry IEO |
40 | Lung cancer, N = 2847 Y = 100 |
rtPCR and FISH | 55.8 | 14.7 | 26.4 | – | – | – | 0 | PI3KA: 2.9 KRAS: 14.7 |
| Ye et al., 2014 Fudan University Shanghai Cancer Centera |
40 | Resected LUAD N = 123 Y = 36 |
rtPCR, FISH for ALK and RET |
69.5 versus 78.2; P = 0.39 | 52.8 versus 63.2; P = 0.13 Ex19: 73.7 versus 49.1 Ex20: 5.3 versus 3.6 Ex21: 21.0 versus 47.3 |
5.6 versus 4.6 | – | 0 versus 3.4 | 2.8 versus 1.1 | 0 versus 2.3 | KRAS: 8.3 versus 3.4 TP53: 72.2 versus 25.3; P < 0.01 LKB1: 11.1 versus 11.5; P = 0.95 |
| VandenBussche et al., 2014 Johns Hopkins Medical Institutions, Baltimore |
50 | NSCLC with molecular testing N = 53 |
pyroPCR and NGS FISH (ALK) |
52.8 | 20 | 11.6 | – | 0 | – | – | KRAS: 25.5 |
| Luo et al., 2018 West China Hospital |
45 | Never-smoking resected LUAD N = 36 |
WGS | 63.9 | 25 | 17 | – | 14 | 8 | – | MET: 14 Mean somatic mutation rate: 4.7 mut/MB. |
| He et al., 2020 Taipei Veterans General Hospitala |
40 | NSCLC N = 5051 Y = 168 |
rtPCR for EGFR IHC for ALK |
22.6 versus 16.2; P = 0.02 | 4.2 versus 0.5; P < 0.01 | – | – | – | – | – | |
| Hou et al., 2020 cBioPortal for Cancer Genomics databasea |
45 | LUAD N = 773 Y = 42 |
NGS | 59.6 versus 33.7; P < 0.01 | 30.9 versus 17.3; P < 0.01 | 9.5 versus 2.8; P = 0.01 | 4.7 versus 1.9; P = 0.05 | 2.3 versus 2.0; P = 0.05 | 9.5 versus 1.0; P < 0.01 | 0 versus 3.0; P = 0.72 | MET: 2.3 versus 5.6; P = 0.06 KRAS: 4.7 versus 32.2; P < 0.01 |
| Zhong et al., 2018 First Affiliated Hospital of Medical College, Zhejiang Universitya |
40 | Lung cancer N = 439 Y = 272 |
rtPCR | – | 41.3 versus 43.9; P = 0.76 EGFR mutation types: P < 0.01 Ex19del: 30.4 versus 14.0 L858R: 8.7 versus 21.1 Other types: 2.2 versus 8.8 Wild type: 58.7 versus 56.1 |
17.0 versus 4.1; P < 0.01 | 0 versus 2.1; P = 0.45 | – | – | – | – |
| Scarpino et al., 2016 Sant'Andrea Hospital of Romea |
50 | LUAD N = 789 Y = 78 |
RtPCR for EGFR FISH for ALK and ROS1 |
– | 12.8 versus 16 | 18 versus 6 | 8.6 versus 1 | – | – | – | – |
ALK, anaplastic lymphoma kinase; APC, adenomatous polyposis coli; BRAF, v-Raf murine sarcoma viral oncogene homolog B; BRCA1, breast cancer type 1; CT, chemotherapy; EGFR, epidermal growth factor receptor; Ex19del, exon 19 deletion; Ex20ins, exon 20 insertion; FISH, fluorescence in situ hybridization; HER2, human epidermal growth factor receptor 2; IEO, Instituto Europeo di Oncologia; IHC, immunohistochemistry; JAK2, Janus quinasa 2; KRAS, Kirsten rat sarcoma viral oncogene homolog; LKB1, Liver Kinase B1; LUAD, lung adenocarcinoma; MB, megabase; MET, mesenchymal epithelial transition receptor; MYC, MYC proto-oncogene; NGS, next-generation sequencing; NSCLC, non-small-cell lung cancer; PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase; RET, rearranged during transfection gene; ROS1, c-ROS oncogene 1; STK11, Serine/Threonine Kinase 11; TP53, tumor protein p53; WES, whole exome sequencing; WGS, whole genome sequencing; Y, young.
a
Comparative studies: young versus old patients.